SS 14 - Pediatrics 2
104 - Impact of Radiation Therapy on Patterns of Relapse and Survival in Children with Stage III Favorable Histology Wilms Tumor
Monday, October 22
11:45 AM - 11:55 AM
Location: Room 008
John Kalapurakal, MD, FASTRO
Northwestern Memorial Hospital
Northwestern University: Professor, Radiation Oncology: Employee
Children's Oncology Group (COG): Chair, Radiation Oncology Discipline
Impact of Radiation Therapy on Patterns of Relapse and Survival in Children with Stage III Favorable Histology Wilms Tumor
J. A. Kalapurakal1, A. C. Paulino2, Y. Y. Chi3, Y. Kim3, L. Ji3, P. F. Ehrlich4, E. J. Perlman5, E. A. Mullen6, J. I. Geller7, G. Khanna8, T. J. FitzGerald9, F. Laurie10, K. Karolczuk11, Z. A. Tochner12, T. E. Hamilton13, K. M. Gow14, R. C. Shamberger13, P. E. Grundy15, J. S. Dome16, and C. V. Fernandez17; 1Northwestern Memorial Hospital, Chicago, IL, 2The University of Texas MD Anderson Cancer Center, Houston, TX, 3University of Florida, Gainesville, FL, 4University of Michigan, Ann Arbor, MI, 5Ann and Robert Lurie Children's Hospital of Chicago, Chicago, IL, 6Dana Farber Cancer Institute, Boston, MA, 7Cincinnati Children's Medical Center, Cincinnati, OH, 8Washington University, St. Louis, MO, 9UMass Memorial Medical Center, Worcester, MA, 10IROC Rhode Island (QARC), Lincoln, RI, 11Imaging and Radiation Oncology Core (IROC), Lincoln, RI, 12University of Pennsylvania, Philadelphia, PA, 13Harvard University, Boston, MA, 14University of Washington, Seattle, WA, 15University of Alberta, Calgary, AB, Canada, 16Children's National Medical Center, Washington, DC, 17Dalhousie University, Halifax, NS, Canada
Purpose/Objective(s): To determine the impact of radiation therapy (RT) on patterns of relapse and survival in children with stage III favorable histology Wilms tumor (FHWT) after multimodality therapy on Children’s Oncology Group (COG) protocol AREN0532.
Materials/Methods: COG study AREN0532 prospectively accrued stage III FHWT pts between 2006 and 2013. All patients were centrally reviewed. All pts were recommended nephrectomy, RT (10Gy to flank/whole abdomen) and chemotherapy (regimen DD4A vincristine, dactinomycin, doxorubicin). All RT records were reviewed and verified centrally. The relation between relapse sites and RT fields was determined. Relapses were classified as either ‘in-RT field’ or ‘out-of-RT field’ or ‘both’. Distant metastases were classified as ‘out-of-RT field’ failures. Statistical methods included log-rank test and Kaplan-Meier estimates of Failure Free Survival (FFS).
Results: 535 pts with a median age of 3.7 yrs were eligible. 52% were female and 70% were Caucasian. 419 pts (78%) had upfront nephrectomy, 96 pts (18%) had loss of heterozygosity LOH at 16q, 56 pts (11%) had LOH at 1p and 71% had no LOH. There were many criteria for stage III designation including delayed nephrectomy (116 pts), lymph node positive (151 pts), margin positive (189 pts) and peritoneal implants (24 pts). 320 pts (60%) had flank RT, and 192 (36%) had Whole Abdomen RT and 2% had combined RT fields. Contrary to protocol guidelines, 10 pts (2%) did not receive RT. RT treatments were per protocol in 85% pts, 7% had minor and 8% had major deviations. After a median follow up of 5 years, the 4 year relapse free and overall survival was 88% and 97% respectively. The in-RT field relapse rate was 2% (11 pts) and the out-of-RT field relapse rate was 10% (54 pts). The sites of out-of-RT field relapses included abdomen (6 pts, 1.1%), lung (35 pts, 6.7%), liver (7 pts, 1.3%) and others (6 pts, 1.1%). The overall abdominal relapse rate was 2% (11 pts) after RT and 30% (3/10 pts) in the no-RT group. The 4 year in-RT field FFS was 99% after flank RT and 96.3% after Whole abdomen RT (P<0.001). The 4 year relapse rates, FFS and P-values for statistically significant prognostic factors are shown below. Patients who did not receive RT were scored NA (not applicable) for in- RT field relapse.
| FACTOR || GROUP || IN-RT FIELD RELAPSE RATE, FFS || P VALUE || OUT-OF-RT FIELD RELAPSE RATE, FFS || P VALUE |
| RT || Yes || 2%, 98% || NA || 10%, 90% || <0.001 |
| No || NA || 40%, 58% |
| LN Invasion || Yes || 3%, 97% || 0.058 || 15%, 85% || 0.001 |
| No || 0.4%, 99.6% || 5%, 95% |
| LOH || Neither || 1%, 99% || 0.007 || 7%, 93% || 0.001 |
| 16q only || 2%, 98% || 17%, 84% |
| 1p only || 9%, 91% || 20%, 80% |
None of the other patient or treatment factors had any influence on relapse rates.
Conclusion: Children with stage III FHWT have good survival outcomes after therapy on COG AREN0532. RT was delivered in 98% of patients with excellent tumor control rates. The significant adverse prognostic factors for higher relapse rates were: 1) not delivering RT, 2) lymph node invasion and 3) LOH at 1p or 16q. These results highlight the importance of RT as an integral part of the multimodality treatment for FHWT.
Author Disclosure: J.A. Kalapurakal: Chair, Radiation Oncology Discipline; Children's Oncology Group (COG). A.C. Paulino: Royalties for text book; Elsevier Inc. Committee Member; ABR. Y. Chi: None. L. Ji: None. P.F. Ehrlich: None. E.A. Mullen: None. G. Khanna: None. T.J. FitzGerald: None. T.E. Hamilton: None. K.M. Gow: None. C.V. Fernandez: None.